Secretion of anterior pituitary hormone undergoes the control by peripheral hormone secreted from target organs for the respective hormones and by secretion-accelerating or secretion-inhibiting hormone from hypothalamus, which is the upper central organ of anterior lobe of pituitary (in this specification, these hormones are collectively called "hypothalamic hormone"). At the present stage, as hypothalamic hormones, nine kinds of hormones including, for example, thyrotropin releasing hormone (TRH) or gonadotropin releasing hormone {GnRH: sometimes called as LH-RH (luteinizing hormone releasing hormone)} are confirmed their existence. These hypothalamic hormones are assumed to show their actions via the receptor which is considered to exist in the anterior lobe of pituitary, and observational studies of receptor genes specific to these hormones, including cases of human, have been developed. Accordingly, antagonists or agonists specifically and selectively control the action of hypothalamic hormone by acting on these receptors and control the secretion of anterior pituitary hormone. As the results, they are expected to be useful for prophylactic and therapeutic agents of anterior pituitary hormone dependent diseases.
As compounds having such GnRH antagonistic activity, a number of compounds including, for example, derivatives of GnRH such as straight-chain peptides (U.S. Pat. No. 5,140,009, U.S. Pat. No. 5,171,835), cyclic hexapeptide derivatives (Japanese Patent Application Laid-open No.S61(1986)-191698) or bicyclic peptide derivatives (Journal of Medicinal Chemistry, Vol.36, pp.3265-3273, 1993). Furthermore, as non-peptide compounds having such GnRH antagonistic activity, compounds described in PCT International Publication No. WO 95/28405 are known.
Such peptide compounds leave many problems including, for example, oral administrability, dosage form, stability of the drug, durability of actions, stability on metabolism. It has been desired to obtain GnRH antagonists which have excellent characteristics of high GnRH antagonistic activity, oral administrability, stability in plasma of blood and durability of actions.
The object of the invention lies in providing novel 4,7-dihydro-4-oxothieno[2,3-b]pyridine derivatives having excellent gonadotropin releasing hormone antagonistic activity.